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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-5-25
pubmed:abstractText
We recently generated a transgenic mouse line with activated polyamine catabolism through overexpression of spermidine/spermine N1-acetyltransferase (SSAT). A detailed analysis of brain polyamine concentrations indicated that all brain regions of these animals showed distinct signs of activated polyamine catabolism, e.g. overaccumulation of putrescine (three- to 17-fold), appearance of N1-acetylspermidine and decreases in spermidine concentrations. In situ hybridization analyses revealed a marked overexpression of SSAT-specific mRNA all over the brain tissue of the transgenic animals. The transgenic animals appeared to tolerate subcutaneous injections of high-dose kainate substantially better as their overall mortality was less than 50% of that of their syngenic littermates. We used the expression of glial fibrillary acidic protein (GFAP) as a marker of brain injury in response to kainate. In situ hybridization analysis with GFAP oligonucleotide up to 7 days after the administration of sublethal kainate doses showed reduced GFAP expression in transgenic animals in comparison with their non-transgenic littermates. This difference was especially striking in the cerebral cortex of the transgenic mice where the exposure to kainate hardly induced GFAP expression. The treatment with kainate likewise resulted in loss of the hippocampal (CA3) neurons in non-transgenic but not transgenic animals. These results support our earlier findings indicating that elevated concentrations of brain putrescine, irrespective whether derived from an overexpression of ornithine decarboxylase, or as shown here, from an overexpression of SSAT, play in all likelihood a neuroprotective role in brain injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
540-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10712633-Acetylation, pubmed-meshheading:10712633-Acetyltransferases, pubmed-meshheading:10712633-Animals, pubmed-meshheading:10712633-Brain, pubmed-meshheading:10712633-Cell Count, pubmed-meshheading:10712633-Cerebral Cortex, pubmed-meshheading:10712633-Excitatory Amino Acid Agonists, pubmed-meshheading:10712633-Glial Fibrillary Acidic Protein, pubmed-meshheading:10712633-Gliosis, pubmed-meshheading:10712633-Hippocampus, pubmed-meshheading:10712633-In Situ Hybridization, pubmed-meshheading:10712633-Kainic Acid, pubmed-meshheading:10712633-Lethal Dose 50, pubmed-meshheading:10712633-Mice, pubmed-meshheading:10712633-Mice, Inbred BALB C, pubmed-meshheading:10712633-Mice, Inbred DBA, pubmed-meshheading:10712633-Mice, Transgenic, pubmed-meshheading:10712633-Nerve Tissue Proteins, pubmed-meshheading:10712633-Neurons, pubmed-meshheading:10712633-Polyamines, pubmed-meshheading:10712633-Putrescine, pubmed-meshheading:10712633-RNA, Messenger
pubmed:year
2000
pubmed:articleTitle
Overexpression of spermidine/spermine N-acetyltransferase in transgenic mice protects the animals from kainate-induced toxicity.
pubmed:affiliation
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, FIN-70211 Kuopio, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't